This proposal will establish proof of concept for the use of nitric oxide (NO) as an effective treatment for diabetic gastroparesis. The NO will be delivered using Amulet's NORTECH nitric oxide releasing technology. NORTECH delivers NO in a predictable and controllable manner, and without the possibility of forming carcinogenic nitrosamines. NORTECH is uniquely able to deliver biologically active levels of NO for a sustained period at gastric pH (2.0), making it an ideal agent to deliver NO to the stomach. The NORTECH will be tested in an animal model of diabetic gastroparesis. The proof of concept will constitute studies that include a determination of the optimal dosing time (i.e. a range of time points from 30 min before meals to 60 min after meals), the establishment of a dose-response relationship and comparison with metoclopramide (a currently used but problematic treatment), and a study of how NO affects the physiological mechanisms of gastric emptying. Successful completion of the specific aims of the proposal will definitively determine the feasibility of using NORTECH as a treatment for gastroparesis. Up to 25% of the global diabetic population suffers from gastroparesis. The disease can cause extreme discomfort, pain, frequent vomiting and leads to a very low quality of life for those who suffer from its effects. Currently there is no adequate treatment. An effective treatment for gastroparesis can significantly benefit the quality of life for those who suffer from the disease. [unreadable] [unreadable] [unreadable]